Lutty G A, Merges C, McLeod D S, Wajer S D, Suzuka S M, Fabry M E, Nagel R L
Wilmer Ophthalmological Institute, Baltimore, MD, USA.
Curr Eye Res. 1998 Apr;17(4):438-44. doi: 10.1080/02713689808951225.
To determine if vascular occlusion and nonperfusion is associated with the outer retinal atrophy, retinopathy, and choroidopathy (chorioretinopathy) that occurs in the alpha H beta S[beta MDD] and alpha H beta S [alpha MD beta MDD] transgenic mouse models of sickle cell disease.
Mice from the alpha H beta S[beta MDD] and alpha H beta S[alpha MD beta MDD] transgenic mouse lines that express high levels of human beta S globin were anesthetized and administered horseradish peroxidase (HRP) intracardially. After 1 min, the animals were sacrificed, and the retina from one eye was excised, fixed, and developed in diaminobenzidine (DAB). The contralateral eye was fixed, embedded whole in glycol methacrylate, and HRP developed in 2.5 microns sections.
HRP reaction product (HRP-RP) and stained erythrocytes (RBCs) (due to endogenous peroxidase) were diffusely distributed within all vascular lumens in flatmount retinas from control animals (littermates homozygous for the mouse Beta Major deletion not expressing the beta S transgene). In 42.5% of the transgenic mice expressing beta S without any proliferative retinopathy, many blood vessels contained RBC plugs and lacked lumenal HRP-RP. In addition to packed RBCs, fibrin was sometimes present at sites of occlusion. In sections from whole eyes of the same animals, foci of photoreceptor degeneration were associated with areas of choriocapillaris nonperfusion (lumen that lacked HRP-PR). In areas with normal photoreceptors, the choriocapillaris appeared perfused (HRP-RP was present). In animals with proliferative chorioretinopathy, some neovascular formations lacked luminal HRP-RP, suggesting autoinfarction.
Nonperfused retinal and choroidal vessels were observed in mice from the alpha H beta S[beta MDD] and alpha H beta S[alpha MD beta MDD] lines without retinal and choroidal neovascularization, whereas, all mice with neovascularization had nonperfused areas. Furthermore, small foci of PR loss were associated with areas of nonperfused choriocapillaris. These results suggest that sickle cell-mediated vaso-occlusions are an initial event in the chorioretinopathy and outer retinal atrophy that occurs in these models.
确定血管闭塞和无灌注是否与镰状细胞病的αHβS[βMDD]和αHβS[αMDβMDD]转基因小鼠模型中发生的外层视网膜萎缩、视网膜病变和脉络膜病变（脉络膜视网膜病变）相关。
对表达高水平人βS珠蛋白的αHβS[βMDD]和αHβS[αMDβMDD]转基因小鼠品系的小鼠进行麻醉，并经心内注射辣根过氧化物酶（HRP）。1分钟后，处死动物，切除一只眼睛的视网膜，固定并在二氨基联苯胺（DAB）中显色。对侧眼睛固定，整体包埋在甲基丙烯酸乙二醇酯中，并在2.5微米切片中进行HRP显色。
在对照动物（不表达βS转基因的小鼠β-珠蛋白主要缺失纯合子同窝仔）的平铺视网膜中，HRP反应产物（HRP-RP）和染色的红细胞（RBC）（由于内源性过氧化物酶）在所有血管腔内呈弥漫性分布。在42.5%未出现任何增殖性视网膜病变的表达βS的转基因小鼠中，许多血管含有红细胞栓子且缺乏管腔内HRP-RP。除了密集的红细胞外，纤维蛋白有时也出现在闭塞部位。在同一只动物的全眼球切片中，光感受器变性灶与脉络膜毛细血管无灌注区域（缺乏HRP-PR的管腔）相关。在光感受器正常的区域，脉络膜毛细血管似乎有灌注（存在HRP-RP）。在患有增殖性脉络膜视网膜病变的动物中，一些新生血管形成缺乏管腔内HRP-RP，提示自动梗死。
在αHβS[βMDD]和αHβS[αMDβMDD]品系的小鼠中观察到无灌注的视网膜和脉络膜血管，且无视网膜和脉络膜新生血管形成，而所有有新生血管形成的小鼠都有未灌注区域。此外，小的光感受器缺失灶与脉络膜毛细血管未灌注区域相关。这些结果表明，镰状细胞介导的血管闭塞是这些模型中脉络膜视网膜病变和外层视网膜萎缩的起始事件。
